Topical glycopyrrolate product

ABSTRACT

This invention relates to a convenient and safe product and method of applying glycopyrrolate topically in order to reduce excessive sweating in localized areas for those who suffer from this condition. This invention also relates to combining oral and topical delivery of glycopyrrolate to reduce excessive sweating and minimize side effects. This invention also relates to a convenient and safe product and method of applying glycopyrrolate topically to areas of compensatory sweating after endoscopic thoracic sympathectomy.

FIELD OF THE INVENTION

[0001] This invention relates to a convenient and safe product andmethod of applying glycopyrrolate topically in order to reduce excessivesweating in localized areas for those who suffer from this condition.This invention also relates to combining oral and topical delivery ofglycopyrrolate to reduce excessive sweating and minimize side effects.This invention also relates to a convenient and safe product and methodof applying glycopyrrolate topically to areas of compensatory sweatingafter endoscopic thoracic sympathectomy.

BACKGROUND OF THE INVENTION

[0002] Hays first reported on the topical application of glycopyrrolatefor facial sweating associated with eating (gustatory sweating). (1, 2)Subsequently others have reported on the use of topical glycopyrrolatefor hyperhidrosis and gustatory sweating. Oral glycopyrrolate has alsobeen used for hyperhidrosis. Glycopyrrolate does not cure any underlyingcauses of hyperhidrosis or gustatory sweating, but reduces or preventsthe resulting excessive sweating.

[0003] Use of glycopyrrolate as an anti-secretagogue in the treatment ofpeptic ulcer disease commenced in Canada in 1961. It continues to beused as an antisialogogue in patients with drooling and as apremedication for anaesthesia to prevent excessive secretions.

[0004] Glycopyrrolate is a quaternary amine, which acts as anantimuscarinic, anticholinergic agent. It does not cross the blood brainbarrier and it penetrates biological membranes slowly and therefore,when given topically leads to very few side effects.

[0005] As with all members of this class, glycopyrrolate should not beused by people with glaucoma or cardiac arrhythmias. Glycopyrrolateshould also not be used by people with bladder obstruction, a rapidheart rate, an allergy to glycopyrrolate, or when pregnant orbreast-feeding.

[0006] For most people sweating is a normal response to heat stress andis important in maintaining body temperature. However, in someindividuals sweating can be excessive and unrelated to heat stress. Thisexcessive sweating can be embarrassing and can severely limit socialactivities. The areas typically involved in excessive perspirationare 1) face including the neck and scalp 2) armpits 3) hands 4) back ofthe knees 5) feet 6) groin, and 7) in the case of compensatory sweating,the trunk.

[0007] Nerve impulses from the brain stimulate sweat glands and causeperspiration. Sometimes the nerves stimulate excessive sweatingunrelated to the normal process of temperature control.

[0008] The use of topical glycopyrrolate has been reported over the past20 years. Here is a table of clinical papers reporting use ofglycopyrrolate and the topical formulation used. Treatment ofHyperhidrosis and Gustatory Sweating Author Year ConcentrationFormulation Notes Hay 1978 0.5 & 1.0% Solution and cream Cottonapplicator used to apply presentations solution. Hay 1982 0.5, 1 & 2%Roll-on solution, Glycopyrrolate crystalized out distilled water used,when concentrations above 2%. pH adjusted to 2.5 to 4.0 Few patientsneed to rub lotion into the skin to get better effects. Hay 1982 2 & 4%HEB cream base Solution worked better than (Barnes- Hind cream. May 19890.5, & 2.0% 0.5 & 2.0% roll-on; almost all patients obtained total 2.0%cream. Used Hays or partial relief. Placebo formulation, treatmentyielded no response. Atkin 1996 0.50% cetamacrogol A Crushed Robinul ™tablets mixed formulation cream base into cream Shaw 1997 0.50%cetamacrogol A formulation cream base Seukeran 1998 2% cetamacrogol ACould not get cream into hairline. formulation cream base Cream andsweat mixture unacceptable. Seukeran 1998 0.50% aqueous solution Workedwell Urman 1999 0.50% Lotion in a roll-on dispenser

[0009] Here are the details from one of these papers. In a recentclinical trial (Shaw, J. E., C. A. Abbott, et al. (1997)) to determineif topical glycopyrrolate is able to control diabetic gustatorysweating, the authors found that topical glycopyrrolate is an acceptablesafe and effective treatment for diabetic gustatory sweating. A placeboor glycopyrrolate 0.5% cream was self administered by hand to the faceand neck. A challenge test was administered, at baseline and at the endof each of the treatment periods. The sweat challenge test measures theamount of sweat produced on the forehead relative to reference sites onthe arm and the leg. Glycopyrrolate treated patients had a statisticallysignificant reduction in sweat production during the challenge test(p=0.008). Daily diary records indicated that topical glycopyrrolatetreatment resulted in a reduction in frequency and severity of gustatorysweating compared to the placebo treatment (p=0.004). One patient out of14 discontinued therapy because of a local skin reaction. No otheradverse effects were reported.

SUMMARY OF THE INVENTION

[0010] This invention relates to a pad containing an amount ofglycopyrrolate in solution, for topical application of a therapeuticallyeffective amount of glycopyrrolate, which is useful in reducing sweatingin humans. In an embodiment of this invention, the solution is a 5 to66% ethanol solution and the amount of glycopyrrolate in solution isgreater than 0.25% and not more than 6%, particularly 1%, 2% or 3%glycopyrrolate, or greater than 2.5 milligrams and not more than 60milligrams of glycopyrrolate.

[0011] In an embodiment of the invention the pad is a 75:25 rayon andpolypropylene pad containing about 1 ml of an about 2%glycopyrrolate/32% ethanol solution for topical application, which isuseful in reducing sweating in humans.

[0012] This invention also relates to a container containing multiplepads of glycopyrrolate comprising a lid that is capable of being easilyopened and closed and functions to prevent evaporation when closed.

[0013] This invention also relates to a use of a pad containing anamount of glycopyrrolate in solution, for topical application of atherapeutically effective amount of glycopyrrolate to any part of thehuman body on which the reduction of sweating is desired, with theexception of mucous membranes.

[0014] This invention also relates to a use of a pad containing anamount of glycopyrrolate in solution, for topical application of atherapeutically effective amount of glycopyrrolate to any part of thehuman body on which the reduction of sweating is desired (with theexception of mucous membranes) in combination with another oral and/ortopical therapy for reduction of sweating.

[0015] This invention also relates to a method of preparing a containerof pads containing a 2% glycopyrrolate solution comprising:

[0016] Mixing 66.7 mL distilled water and 33.3 mL 95% ethanol togetherto form an ethanol solution;

[0017] Adding 2 grams of glycopyrrolate powder to said ethanol solutionand stirring until completely dissolved;

[0018] Adjusting the pH level of said glycopyrrolate solution to 4.0with hydrochloric acid;

[0019] Pouring 30 to 36 mL of said glycopyrrolate solution onto the toppad of a container of 30 rayon/polypropylene pads; and

[0020] Covering the container with a resealable lid.

DESCRIPTION

[0021] Introduction

[0022] Excessive sweating can cause embarrassment in social situationsand an effective treatment is desirable. Glycopyrrolate has been usedorally and topically in the past to reduce excessive sweating. Asindicated above, glycopyrrolate has been formulated for topical use as acream, solution and roll-on, and has been applied using a cotton swab asan applicator.

[0023] Using the previously available delivery methods, the topicalapplication of glycopyrrolate can be messy and inconvenient. Oraltreatment is simple to administer, however, oral treatment has systemiceffects and this causes increased side effects.

[0024] Accordingly, the inventors developed a new topical deliveryproduct and method for glycopyrrolate, namely glycopyrrolate on pads. Aswell, the inventors combined the use of topical glycopyrrolate with oralglycopyrrolate to achieve maximum sweat control and minimal sideeffects.

[0025] Use of Invention

[0026] The topical application of glycopyrrolate is especiallyconvenient for those patients who have localized sweating of the faceand hands. This invention provides a convenient and safe method to applyglycopyrrolate to the skin in order to reduce excessive sweating inlocalized areas in those who suffer from this condition. The presentinvention of glycopyrrolate pads has benefits over previously usedtopical glycopyrrolate as follows:

[0027] 1. Ease of application;

[0028] 2. Coverage of large flat surface such as face and neck (roll-onapplies narrow band);

[0029] 3. Rubbing or massaging formulation into skin for better efficacy(Hays 1982 showed this gave better efficacy in some patients);

[0030] 4. Applying approximately the same amount of medication at eachuse;

[0031] 5. A formulation that will allow application into the hairline atthe margins of the face since in gustatory sweating, facial sweatingextends into the hairline;

[0032] 6. A rapidly drying non-greasy, residue free formulation thatpermits the applications of cosmetics over top;

[0033] 7. A hypoallergenic formulation containing no known allergens,unless a preservation agent (antibacterial or chemical stabilizer) isadded, as may be required for commercial formulations; and

[0034] 8. A formulation that can be prepared in a wide range ofstrengths to accommodate the variability of glycopyrrolate absorptionbetween different individuals; (Hays 1982, Rautakorpi 1998, provideevidence in their clinical paper on variable absorption)

[0035] 9. Convenient to use on the spot before certain events, forexample to reduce sweating on the palms to enhance performance insituations such as golf or baseball etc, and to reduce sweating insituations such as business presentations and performing arts.

[0036] A surgical procedure called endoscopic thoracic sympathectomy(ETS), the cutting or clipping of fibers of the sympathetic nervoussystem, is also used to treat the condition of excessive sweating. Oneof the side effects of this procedure is compensatory sweating inadjacent areas not affected by the surgical procedure. The presentinvention provides a convenient and safe method of applyingglycopyrrolate topically for those patients with areas of compensatorysweating after endoscopic thoracic sympathectomy.

[0037] For those with excessive sweating over a very large body surfacearea and severe sweating in localized areas such as the hands, feet andface, a combination of oral and topical delivery of glycopyrrolateprovides the best balance of sweat control and minimizing side effects.This invention also relates to combining oral and topical delivery ofglycopyrrolate to reduce excessive sweating and minimize side effects.

[0038] Oral glycopyrrolate reduces excessive sweating, but in somepatients localized problem areas e.g. hands or feet still remain. To getcomplete control the patient may not wish to increase the oral dosebecause then the side effects become intolerable. Topical glycopyrrolateapplied locally to the problem spots improves the over all control ofhyperhidrosis. Because of its local application, it does not result inadditional side effects. Use of the invention can also be combined withother forms of topical glycopyrrolate, such as, glycopyrrolate in gel orcream form or a metered spray of a solution of glycopyrrolate.

[0039] Some patients have excessive sweating of the hands and trunk.(There are other combinations such as face, hands and trunk or hands andfeet etc.) The hands, face, feet and axilla are usually worse than thetrunk. Topical application works well for the local areas (hands, face,feet, axilla). But, areas such as the back may not be as accessible forself-application. If the surface area is too difficult or too large tocover with the topical product, the addition of an oral preparationhelps to treat hyperhidrosis more effectively than topical alone.

[0040] Finally, the topical glycopyrrolate invention may be used as anantiperspirant for individuals who experience ordinary sweating. Suchuse may be over the body, but it is particularly effective on theunderarms. Sweating is a normal body response and use on only theunderarms is recommended for those who experience ordinary sweating. Inthis way, the body's normal sweat production is not impeded anywhere butthe underarm and potential side effects are minimized.

[0041] The topical glycopyrrolate invention may incorporate perfumes,scents, preservation agents, moisturizers and the like, as are found inunderarm deodorants, provided that such additives do not compromise theeffectiveness of the glycopyrrolate.

[0042] Development of Invention

[0043] Formulations Examined

[0044] In order to provide an improved topical formulation, awater-based formulation was desired. Glycopyrrolate dissolves readily inwater. However, alcohol was added to the formulation to improve thespeed of drying. Glycopyrrolate also dissolves readily in alcohol. Sometested formulations and results were as follows:

[0045] 1. A 100% distilled water formulation was too slow in drying whenapplied to the skin

[0046] 2. A mixture of 33.3 % distilled water and 66.7% of 95% ethanol,evaporated rapidly but caused excessive drying. A bitter tasting residuewas left on the skin.

[0047] 3. A mixture of 66.7% distilled water and 33.3% of 95% ethanoldried faster than 100% distilled water but did not cause the dryingassociated with the solution containing 66.7% of 95% ethanol.

[0048] A solution of 66.7% distilled water and 33.3% of 95% ethanol waschosen to deliver the glycopyrrolate. However, any solution which meetsthe criteria of dissolving glycopyrrolate, being absorbed by anapplication pad, and quick drying without causing harm to the skin, canbe used.

[0049] A concentration of glycopyrrolate greater than 0.1% is desirablesince 0.1% has been shown to be ineffective (Hays 1978). A 1%glycopyrrolate solution was initially chosen for testing purposes.However, the range of glycopyrrolate can vary to meet the needs of thepatient. The upper limit could be at least as high as 6%, although mildside effects begin to present themselves after 4% (Hays 1978).

[0050] Preparation of 100 mL Solution of 1% Glycopyrrolate

[0051] A 1% glycopyrrolate solution was made by dissolvingglycopyrrolate powder in the 66.7 mL distilled water and 33.3 mL of 95%ethanol solution.

[0052] Take water 66.7 mL

[0053] Add 95% ethanol 33.3 mL

[0054] Adjust pH to 4.0 (range 3.5 to 4.5) with a few drops ofhydrochloric acid

[0055] Add 1 gram of glycopyrrolate stir until glycopyrrolate completelydissolved.

[0056] To make 2% solution add 2 gram glycopyrrolate instead of 1 grametc.

[0057] The resulting solution of glycopyrrolate contains approximately31.635% of ethanol. To avoid skin irritation, the pH of the formulationshould be close to that of the skin (pH 5.5). For the chosen 66.7%/33.3%distilled water/95% ethanol solution, the pH level was adjusted to 4.0with hydrochloric acid. The pH of 4.0 was chosen for stability of thesolution and to be as close to the pH of the skin (pH 5.5) as possible.

[0058] Application Pads Tested

[0059] The inventors discovered that glycopyrrolate could be deliveredeffectively using pads. The patient could easily and quickly apply theglycopyrrolate with a pad, which allowed the glycopyrrolate to bemassaged into the skin for improved results.

[0060] Cotton Cosmetic Pads

[0061] Here is the experiment conducted to determine the absorbency ofcotton cosmetic pads. Calculated amount of Weight of glycopyrrolate Dryweight of Wet weight of solution (assuming a Solution pad in grams padabsorbed 1% solution Water 0.53 7.98 7.4 74 mg

[0062] These cotton cosmetic pads absorbed too much liquid making itdifficult to control the application of the solution to the skin.

[0063] 75% Rayon/25% Polypropylene Pads

[0064] Here is the experiment to determine the absorbency ofrayon/polypropylene pads, using the brand of Kleentest™ #9807 2.125diameter pads, comprised of 75% rayon and 25% polypropylene by weight.Calculated amount of Average weight glycopyrrolate Average dry Averagewet of solution (assume 1% Solution weight (N = 10) weight (N = 10)absorbed (N = 10) solution) Water 0.196 1.393 1.197 11.9 mg 33.3% 95%0.192 1.219 1.027 10.3 mg Ethanol/66.7% Water 66.7% 95% 0.195 1.0340.839  8.4 mg ethanol/33.3% Water

[0065] These pads hold about 1 mL of liquid, are easy to apply to skin,and do not drip.

[0066] These pads impregnated with 1% glycopyrrolate solution of66.7%/33.7% distilled water/95% ethanol contain about 10 mg ofglycopyrrolate.

[0067] Variability in Pad Content Due to Stacking

[0068] The effectiveness of the glycopyrrolate solution on a pad alsodepends on whether the invention can be delivered to the patient foruse. Several pads must be packaged in such a way that each individualpad delivers a desirable amount of glycopyrrolate.

[0069] The brand of Kleentest™ #9807 2.125 diameter pads are packagedfor consumer use in stacks of 30. Tests were conducted to determinewhich solution would give the best content uniformity in each pad fromtop of the stack to the bottom of the stack. A 1% solution was desiredfrom the above experiment.

[0070] The following experiment was conducted to determine if aconsistent amount of glycopyrrolate was delivered per pad. Thirty tothirty-six ml of solution were added to ajar containing a stack of 30 ofthe brand of Kleentest™#9807 2.125 diameter pads. The average weight ofthe top six pads was compared to the bottom 6 pads. 33.3% 95% Ethanol/66.7% 95% Ethanol/ Solution Water 66.7% Water 33.3% Water Av Net Wt Top6 1.08 g 0.95 0.84 Av Net Wt 1.31 g 1.11 0.9 Bottom 6 Difference 18% 15%7%

[0071] The 66.7% 95% ethanol/33.3% water solution yields the smallestpercent variation from the average of the top 6 pads to the average ofthe bottom 6 pads. Increasing the water content to 66.7 and 100%increases the percent variation from 15% to 18%, respectively.

[0072] Preferred Invention of Glycopyrrolate on Pads

[0073] Other pads may be used as effectively if they meet the followingcriteria:

[0074] 1. Pads made of a material able to hold about 1 mL of solution.

[0075] 2. Solution containing from 0.25% to 6% glycopyrrolate.

[0076] 3. Aqueous solution having an ethanol content greater than 5% andless than 66%.

[0077] 4. May also contain suitable preservatives, anti-fungals,anti-bacterials and perfumes.

[0078] Use of Glycopyrrolate Pads

[0079] Take one pad and apply to the affected area once daily. Ifrequired a second pad may be used for large surface areas.

[0080] Directions for using on face, hands, feet or armpits:

[0081] 1. Remove a single pad from the jar.

[0082] 2. Wipe affected area as desired.

[0083] 3. Apply any cosmetics or creams only after the applied liquidhas dried.

[0084] 4. Do not wash the treated area for at least 4 hours.

[0085] 5. Avoid applying to mouth, eyes or mucous membranes. Contactlens users: Insert contact lens before handling glycopyrrolate pads orwash hands thoroughly before inserting lens.

[0086] 6. Do not apply to cut or broken skin.

[0087] 7. Discontinue use if rash or skin irritation develops.

[0088] 8. Keep product away from children and pets.

[0089] 9. Close container firmly after use to prevent evaporation.Protect from heat.

EXAMPLES OF PATIENT RESPONSES TO GLYCOPYRROLATE PADS

[0090] The following examples show how the invention has worked forindividual patients, that is, delivering a therapeutically effectiveamount of glycopyrrolate to reduce sweating, and how it can be adjustedfor any patient. For instance, if a patient is finding that the topicalpads of glycopyrrolate of the invention provide acceptable reduction insweating but experiences side effects such as dry mouth, the strength ofthe glycopyrrolate in solution can be reduced to provide the bestresults without side effects. Conversely, if sweating has not beenreduced to acceptable levels, the strength of the glycopyrrolate insolution can be increased.

[0091] Topically applied glycopyrrolate penetrates the skin over thesweat glands and acts as a shield preventing over-stimulation of thesweat glands. The effectiveness of the topical glycopyrrolate inventiondepends on the amount of nerve stimulation each individual brainproduces, the thickness of the skin over the sweat glands and theconcentration of glycopyrrolate. Most patients enjoy effective controlof sweating using the regular strength of 2% glycopyrrolate, however,personalized strength pads can be prepared to maximize the benefit fromthe treatment.

[0092] Generally topical glycopyrrolate should be made in the range of a0.25% to 6% solution to deal with individual variability in penetrationof biological membranes.

[0093] 1. A 35 year old, male patient with excessive forehead and groinsweating resulting in a facial rash and fungal infection was advised totry the invention. The patient was started on a 1% pad. After 2 weeksthe patient reported that the glycopyrrolate pads had worked so wellthat they had changed his life. His facial and groin sweating hadimproved markedly and as a result the chronic fungal infection of hisgroin and constant facial rash had both improved. He was able toparticipate in social situations that previously would have made himfeel very uncomfortable. The patient experienced no side effects whileusing the 1% strength glycopyrrolate pads. The patient wished to reducehis residual sweating. The patient is now using used 1.5% strengthglycopyrrolate pads and has obtained satisfactory control of hissweating. He has not experienced any side effects.

[0094] 2. A 50 year old, male patient with excessive facial sweating wassearching for an alternative to oral therapy. The patient had beentaking up to 6, 15 mg capsules per day of propanthaline, an oralanticholinergic. The patient was started on 1% strength glycopyrrolatepads then moved to 2% strength glycopyrrolate pads and finally 3%strength glycopyrrolate pads. The 3% strength glycopyrrolate pads gavethe patient almost complete control of his facial sweating. The patientdid not experience any side effects while using 3% strengthglycopyrrolate pads. The patient only occasionally uses oralpropantheline.

[0095] 3. A 40 year old male, suffering from excessive facial and scalpsweating began using 1% strength glycopyrrolate pads on his face. He wasable to control his facial sweating. At the time of re-ordering the 1%strength glycopyrrolate pads, he asked if there was a more efficientmanner for him to apply the medication to the top and back of his scalp.The pad was not allowing him to penetrate his strands of hair to applythe medication directly to his scalp. He was provided with a 1% solutionof glycopyrrolate in water and ethanol in a metered spray container. Thepatient uses the spray to apply the glycopyrrolate solution to hisscalp. The 1% glycopyrrolate solution in a metered spray bottle was ableto satisfactorily reduce his scalp sweating. The patient also uses 1%strength glycopyrrolate pads to control his facial flushing. The patienthas not experienced any side effects with the topical application ofglycopyrrolate.

[0096] Bibliography

[0097] 1. Hays, L. L. (1978). “The Frey syndrome: a review and doubleblind evaluation of the topical use of a new anticholinergic agent.”Laryngoscope 88(11): 1796-824.

[0098] 2. Hays, L. L., A. J. Novack, et al. (1982). “The Frey syndrome:a simple, effective treatment.” Otolaryngol Head Neck Surg 90(4):419-25.

[0099] 3. Abell, E. and K. Morgan (1974). “The treatment of idiopathichyperhidrosis by glycopyrronium bromide and tap water iontophoresis.” BrJ Dermatol 91(1): 87-91.

[0100] 4. Ali-Melkkila, T., T. Kaila, et al. (1989). “Glycopyrrolate:pharmacokinetics and some pharmacodynamic findings.” Acta AnaesthesiolScand 33(6): 513-7.

[0101] 5. Atkin, S. L. and P. M. Brown (1996). “Treatment of diabeticgustatory sweating with topical glycopyrrolate cream.” Diabet Med 13(5):493-4.

[0102] 6. Berrios, R. J. and P. D. Quinn (1986). “Frey's syndrome:complication after orthognathic surgery.” Int J Adult OrthodonOrthognath Surg 1(3): 219-24.

[0103] 7. Bronshvag, M. M. (1978). “Spectrum of gustatory sweating, withespecial reference to its presence in diabetics with autonomicneuropathy.” Am J Clin Nutr 31(2): 307-9.

[0104] 8. May, J. S. and W. F. McGuirt (1989). “Frey's syndrome:treatment with topical glycopyrrolate.” Head Neck 11(1): 85-9.

[0105] 9. Rautakorpi, P., T. Manner, et al. (1998). “Pharmacokineticsand oral bioavailability of glycopyrrolate in children.” PharmacolToxicol 83(3): 132-4.

[0106] 10. Seukeran, D. C. and A. S. Highet (1998). “The use of topicalglycopyrrolate in the treatment of hyperhidrosis.” Clin Exp Dermatol23(5): 204-5.

[0107] 11. Shaw, J. E., C. A. Abbott, et al. (1997). “A randomisedcontrolled trial of topical glycopyrrolate, the first specific treatmentfor diabetic gustatory sweating.” Diabetologia 40(3): 299-301.

[0108] 12. Sheehy, T. W. (1991). “Diabetic gustatory sweating.” Am JGastroenterol 86(10): 1514-7.

[0109] 13. Stern, L. M. (1997). “Preliminary study of glycopyrrolate inthe management of drooling.” J Paediatr Child Health 33(1): 52-4.

[0110] 14. Stuart, D. D. (1978). “Diabetic gustatory sweating.” AnnIntern Med 89(2): 223-4.

[0111] 15. Urman, J. D. and A. M. Bobrove (1999). “Diabetic gustatorysweating successfully treated with topical glycopyrrolate: report of acase and review of the literature.” Arch Intern Med 159(8): 877-8.

I claim:
 1. A pad containing an amount of glycopyrrolate in solution,for topical application of a therapeutically effective amount ofglycopyrrolate, which is useful in reducing sweating in humans.
 2. Thepad of claim 1 in which said solution is an ethanol solution.
 3. The padof claim 2 in which said solution is a 5% to 66% ethanol solution. 4.The pad of claim 3 in which said solution is about a 32% ethanolsolution.
 5. The pad of claim 1 in which said amount of glycopyrrolatein solution is an amount greater than 0.25% and not more than 6%.
 6. Thepad of claim 5 in which said amount of glycopyrrolate in solution is 1%,2% or 3%.
 7. The pad of claim 1 in which said amount of glycopyrrolatein solution is at least 2.5 milligrams and not more than 60 milligrams.8. The pad of claim 1 in which said pad is comprised of rayon andpolypropylene.
 9. The pad of claim 8 in which the ratio of rayon andpolypropylene is 75:25 by weight.
 10. A rayon and polypropylene padcontaining about 1 ml of an about 2% glycopyrrolate/32% ethanol solutionfor topical application, which is useful in reducing sweating in humans.11. A container containing multiple pads of claim
 1. 12. The containerof claim 11, which additionally comprises a lid that is capable of beingeasily opened and closed and functions to prevent evaporation whenclosed.
 13. A use of a pad containing an amount of glycopyrrolate insolution, for topical application of a therapeutically effective amountof glycopyrrolate to any part of the human body on which the reductionof sweating is desired, with the exception of mucous membranes.
 14. Theuse claimed in claim 13, in combination with another oral and/or topicaltherapy for reduction of sweating.
 15. A method of preparing a containerof pads containing a 2% glycopyrrolate solution comprising: a. Mixing66.7 mL distilled water and 33.3 mL 95% ethanol together to form anethanol solution; b. Adding 2 grams of glycopyrrolate powder to saidethanol solution and stirring until completely dissolved; c. Adjustingthe pH level of said glycopyrrolate solution to 4.0 with hydrochloricacid; d. Pouring 30 to 36 mL of said glycopyrrolate solution onto thetop pad of a container of 30 rayon/polypropylene pads; and e. Coveringthe container with a resealable lid.